Interleukin‐9 deficiency affects lipopolysaccharide‐induced macrophage‐related oxidative stress and myocardial cell apoptosis via the Nrf2 pathway both in vivo and in vitro

Abstract

Previous studies showed that interleukin‐9 (IL‐9) is involved in cardiovascular diseases, including hypertension and cardiac fibrosis. This study aimed to investigate the role of IL‐9 in lipopolysaccharide (LPS)‐induced myocardial cell (MC) apoptosis. Mice were treated with LPS, and IL‐9 expression was measured and the results showed that compared with WT mice, LPS‐treated mice exhibited increased cardiac Mø‐derived IL‐9. Additionally, the effects of IL‐9 deficiency (IL‐9−/−) on macrophage (Mø)‐related oxidative stress and MC apoptosis were evaluated, the results showed that IL‐9 knockout significantly exacerbated cardiac dysfunction, inhibited Nrf2 nuclear transfer, promoted an imbalance in M1 and M2 Møs, and exacerbated oxidative stress and MC apoptosis in LPS‐treated mice. Treatment with ML385, a specific nuclear factor erythroid‐2 related factor 2 (Nrf2) pathway inhibitor significantly alleviated the above effects in LPS‐treated IL‐9−/− mice. Bone marrow‐derived Møs from wild‐type (WT) mice and IL‐9−/− mice were treated with LPS, and the differentiation and oxidative stress levels of Møs were measured. The effect of Mø differentiation on mouse MC apoptosis was also analyzed in vitro. The results showed that LPS‐induced M1 Mø/M2 Mø imbalance and Mø‐related oxidative stress were alleviated by IL‐9 knockout but were exacerbated by ML385 treatment. The protective effects of IL‐9 deficiency on the MC apoptosis mediated by LPS‐treated Møs were reversed by ML‐385. Our results suggest that deletion of IL‐9 decreased the nuclear translocation of Nrf2 in Møs, which further aggravated Mø‐related oxidative stress and MC apoptosis. IL‐9 may be a target for the prevention of LPS‐induced cardiac injury.

Nrf2 attenuates methamphetamine-induced myocardial injury by regulating oxidative stress and apoptosis in mice

“…Several studies have suggested that activation of Nrf2 induces up-regulation of antioxidant target gene expression, leading to a decrease in intracellular oxidative stress, thereby inhibiting myocardial cell apoptosis. 41,42 Nrf2 knockout mice are reported to show more severe phenotypes in disease models than wild-type mice, 43,44 as found in the current study. Notably, knockout of Nrf2 aggravated the degree of myocardial cell apoptosis, while activation of Nrf2 attenuated the degree of myocardial cell apoptosis.…”

Sestrin2 Is Increased in Calcific Aortic Disease and Inhibits Osteoblastic Differentiation in Valvular Interstitial Cells via the Nuclear Factor E2–related Factor 2 Pathway

“…: HY-100523), a specific Nrf2 pathway inhibitor. 18 Then, oxidative stress was measured, including ROS levels, total SOD activity, GSH levels, and MDA levels. Finally, U937 macrophages were pretreated with si-Sesn2, cDNA-Sesn2, or ML385 and then co-cultured with VICs for 24 hours.…”

The Impact of Physical Exercise on Obesity in a Cohort of Southern Italian Obese Children: Improvement in Cardiovascular Risk and Immune System Biomarkers

“…Low CRP levels result in low permeability of the vascular wall to LDL, thus reducing the risk of cardiovascular disease (CVD) [26]. IL-8 and IL-9 are pro-inflammatory cytokines implicated in the pathogenesis of atherosclerosis, with an increased risk of developing cardiovascular disease [27][28][29]. Studies show that exercise involves a decrease in plasma levels of IL-8 and IL-9, with a protective anti-inflammatory effect of exercise compared to atherosclerotic risk [30,31].…”